Few biologists have acquired the kind of celebrity status that James Watson and Francis Crick did.
Their discovery of the double helical structure of the DNA molecule in 1953 is considered one of the biggest breakthroughs in Science, which not only enhanced understanding of how life replicates itself, but also profoundly impacted fields ranging from health to agriculture. So much so that the figure of the twisted ladder structure of the DNA has become a shorthand to represent Science itself. Last week, Watson died at 97.
Early success
Born in the US, Watson was less than 25 years old when he partnered with Crick to unveil the structure of the DNA (deoxyribonucleic acid). The Nobel Prize-winning discovery revealed how individual traits are passed on from one generation to another, and is often placed alongside the development of quantum theory and the theory of gravitation as the greatest scientific accomplishments of the 20th century.
While those theories uncovered the workings of the universe, the DNA discovery was about looking inwards. DNA is a large molecule containing the genetic information of an individual. This information, encoded in the genes, determines all the individual characteristics of the organism — from physical appearance to internal biology. During reproduction, these genes are replicated and transmitted to the offspring, sometimes with small changes that lead to genetic diversity and drive evolution.
The chemical existence of DNA was discovered in 1869 by the Swiss chemist Friedrich Miescher. Decades later, it was learnt that chromosomes, made of DNA and some proteins, were associated with inheritance. By the 1940s, scientists figured out that it was DNA, and not the proteins inside the chromosomes that carried genetic information. But scientists still did not know how DNA was able to store genetic information or how it was passed on. Thus, its structure had to be deciphered.
The breakthrough
In 1952, Watson and Crick experimented with three-dimensional wooden models to fit into a structure that matched the information provided by other scientists.
Clues came through chemical analysis and images obtained from X-ray crystallography methods. Under British chemist Rosalind Franklin’s supervision, her student Raymond Gosling took a historic X-ray photograph (called Photo 51), which showed the double-helix structure of DNA. Watson and Crick saw this photo and some of her unpublished data, which served as the basis of their DNA model. While Franklin was not awarded the Nobel, Crick said after she died in 1958 that her contribution was critical.
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Photo 51, showing X-ray diffraction pattern of DNA. (Wikimedia Commons)
The final Watson-Crick wooden model had two long strands, each with a series of four nitrogen-containing compounds — Adenine (A), Thymine (T), Cytosine (C) and Guanine (G) — held in a chain by some sugar and phosphate compounds. The Adenine on one strand is always opposite the Thymine on the other, while the Cytosine is paired opposite Guanine. The two parallel strands were shaped in a twisted ladder of sorts, to account for stability, compactness and other features revealed in earlier experiments.
The double helix was a rather unintuitive and unique structure for a molecule, but it made sense with all the evidence. “It was quite a moment. We felt sure that this was it. Anything that simple, that elegant just had to be right. What got us most excited was the complementarity of the base sequences (nitrogen-based compounds A, T, C and G) along the two chains. If you knew the sequence – the order of bases – along one chain, you automatically knew the sequence along the other,” Watson wrote in his book DNA: The Story of Genetic Revolution.
Molecular biologist J Gowrishankar, former director of IISER Mohali, said the most beautiful aspect of the structure was that it clearly showed how the genetic information could be replicated accurately and passed on. “The two strands could get separated, and the information on each one was enough to build a separate second strand for itself. It just made it so easy to understand how the replication of genetic information occurs, and how those are passed on,” he said.
The impact
The discovery of the DNA structure sparked a flurry of new research, birthing fields like molecular biology, biotechnology, gene modification and editing.
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Scientists have uncovered how changes in the process of copying genetic information result in some diseases and disorders, and have found fixes through tools like CRISPR. It has had transformational impacts on agriculture, health and industry. Genetic analysis has become a common tool with applications in tracing heredity, forensics and crime, and deciphering the very origin and evolution of organisms.
